Abstract

Background

Regardless of infection route, the intestine is the primary site for HIV-1 infection
establishment and results in significant mucosal CD4+ T lymphocyte depletion, induces
an inflammatory state that propagates viral dissemination, facilitates microbial translocation,
and fosters establishment of one of the largest HIV reservoirs. Here we test the prediction
that HIV infection modifies the composition and function of the mucosal commensal
microbiota.

Results

Rectal mucosal microbiota were collected from human subjects using a sponge-based
sampling methodology. Samples were collected from 20 HIV-positive men not receiving
combination anti-retroviral therapy (cART), 20 HIV-positive men on cART and 20 healthy,
HIV-negative men. Microbial composition of samples was analyzed using barcoded 16S
Illumina deep sequencing (85,900 reads per sample after processing). Microbial metagenomic
information for the samples was imputed using the bioinformatic tools PICRUST and
HUMAnN. Microbial composition and imputed function in HIV-positive individuals not
receiving cART was significantly different from HIV-negative individuals. Genera including
Roseburia, Coprococcus, Ruminococcus, Eubacterium, Alistipes and Lachnospira were depleted in HIV-infected subjects not receiving cART, while Fusobacteria, Anaerococcus, Peptostreptococcus and Porphyromonas were significantly enriched. HIV-positive subjects receiving cART exhibited similar
depletion and enrichment for these genera, but were of intermediate magnitude and
did not achieve statistical significance. Imputed metagenomic functions, including
amino acid metabolism, vitamin biosynthesis, and siderophore biosynthesis differed
significantly between healthy controls and HIV-infected subjects not receiving cART.

Conclusions

HIV infection was associated with rectal mucosal changes in microbiota composition
and imputed function that cART failed to completely reverse. HIV infection was associated
with depletion of some commensal species and enrichment of a few opportunistic pathogens.
Many imputed metagenomic functions differed between samples from HIV-negative and
HIV-positive subjects not receiving cART, possibly reflecting mucosal metabolic changes
associated with HIV infection. Such functional pathways may represent novel interventional
targets for HIV therapy if normalizing the microbial composition or functional activity
of the microbiota proves therapeutically useful.